Human immunodeficiency virus type-1 (HIV-1) Pr55gag virus-like particles are potent activators of human monocytes.
Human immunodeficiency virus type-1 (HIV-1) Pr55(Gag) virus-like particles (VLP) represent an interesting HIV vaccine component since they stimulate strong humoral and cellular immune responses. We demonstrated that VLP expressed by recombinant baculoviruses activate human PBMC to release pro-inflammatory (lL-6, TNF-alpha), anti-inflammatory (IL-10) and Th1-polarizing (IFN-gamma) cytokines as well as GM-CSF and MIP-1alpha in a dose-and time-dependent manner. Herein, residual baculoviruses within the VLP preparations showed no or minor effects. Monocytes could be identified as a main target for VLP to induce cytokine production. Furthermore, VLP-induced monocyte activation was shown by upregulation of molecules involved in antigen presentation (MHC II, CD80, CD86) and cell adhesion (CD54). Exposure of VLP to serum inactivates its capacity to stimulate cytokine production. In summary, these investigations establish VLP as strong activators of PBMC and monocytes therein, potently enhancing their functionality and potency to promote an efficient immune response. This capacity makes VLP an interesting component of combination vaccines.
Speth
Cornelia
C
Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, Innsbruck, Austria.
Bredl
Simon
S
Hagleitner
Magdalena
M
Wild
Jens
J
Dierich
Manfred
M
Wolf
Hans
H
Schroeder
Josef
J
Wagner
Ralf
R
Deml
Ludwig
L
D051940:B7-2 Antigen / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D015497:HIV-1 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D009000:Monocytes / Q000276:immunology*; D009842:Oligopeptides / Q000096:biosynthesis; D011498:Protein Precursors / Q000276:immunology*; D011971:Receptors, Immunologic / Q000096:biosynthesis; D022701:Virosomes / Q000276:immunology*
D051940:B7-2 Antigen; C530950:CD80-CAP; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D009842:Oligopeptides; D011498:Protein Precursors; D011971:Receptors, Immunologic; D022701:Virosomes; C059767:p55 gag precursor protein, Human immunodeficiency virus 1